Cyclooxygenase is an enzyme that catalyzes the addition of two oxygen molecules to arachidonic acid isolated from a phospholipid in a cell membrane by phospholipase A.sub.2 to synthesize prostaglandin G.sub.2, and is a rate-determining enzyme in the synthetic system of prostaglandins such as prostaglandin E.sub.2 and thromboxane B.sub.2. Since Vane reported in 1971 that non-steroidal anti-inflammatory drugs such as aspirin and indomethacin inhibit the cyclooxygenase activity to inhibit the production of prostaglandin E.sub.2, thereby manifesting an anti-inflammatory effect, many non-steroidal anti-inflammatory drugs have been developed by pharmaceutical companies. However, most of the non-steroidal anti-inflammatory drugs inhibit the production of not only prostaglandin E.sub.2 in an inflammatory site but also prostaglandin E.sub.2 having a mucosa-protecting effect in digestive tracts, so that they have a stomach and intestine-damaging effect, and this side effect offers a clinical problem.
In recent years, it has been reported that subtype enzymes exist in the cyclooxygenase. Cyclooxygenase 1 conventionally known always manifests itself in cells of the gastric mucosa, seminal vesicle, platelet and the like and is considered to participate in the maintenance of homeostasis in the living body. On the other hand, cyclooxygenase 2 newly discovered is induced by stimulating a cell participating in inflammation such as a macrophage or synovial cell by a cytokine or the like and is hence considered to participate in an inflammatory reaction. The non-steroidal anti-inflammatory drugs clinically used at present are considered to inhibit not only cyclooxygenase 2 but also the cyclooxygenase 1 activity, thereby bringing about an anti-inflammatory effect and at the same time inducing gastrointestinal disorders.
Therefore, it is expected to develop a drug specifically inhibiting the cyclooxygenase 2 activity as a novel anti-inflammatory agent.
Accordingly, it is an object of the present invention to provide a drug which has an effect of specifically inhibiting the cyclooxygenase 2 activity, and an anti-inflammatory agent scarcely having a stomach and intestine-damaging effect.